IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ http://www.ebi.ac.uk/ miled-2007-2 Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. in vitro In vitro enzymatic study enzymatic study predetermined predetermined participant predetermined Miled N., Yan Y., Hon WC., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson HJ., Backer JM., Williams RL. Synapse - Interactions of proteins with an established role in the presynapse. Multiple anomalous dispersion (MAD) data sets were collected at 100K on ESRF beamline ID14-4 using an ADSC CCD detector. rlw@mrc-lmb.cam.ac.uk,backer@aecom.yu.edu Science (0036-8075) 2007 Only protein-protein interactions imex curation Cancer - Interactions investigated in the context of cancer miled-2007-1 Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Miled N., Yan Y., Hon WC., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson HJ., Backer JM., Williams RL. Synapse - Interactions of proteins with an established role in the presynapse. Multiple anomalous dispersion (MAD) data sets were collected at 100K on ESRF beamline ID14-4 using an ADSC CCD detector. rlw@mrc-lmb.cam.ac.uk,backer@aecom.yu.edu Science (0036-8075) 2007 Only protein-protein interactions imex curation Cancer - Interactions investigated in the context of cancer p85a_human Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 GRB1 Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha protein protein human Homo sapiens Human MSAEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGRKKISPPTPKPRPPRPLPVAPGSSKTEADVEQQALTLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNTENLIKVIEILISTEWNERQPAPALPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLAQYNPKLDVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLGNENTEDQYSLVEDDEDLPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYAQQRR 1-phosphatidyl-1d-myo-inositol 1-phosphatidyl-1D-myo-inositols small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) pk3ca_bovin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Phosphoinositide-3-kinase catalytic alpha polypeptide Serine/threonine protein kinase PIK3CA PIK3CA Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha protein protein bovin Bos taurus (Bovine) Bovine MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN pik3ca-1_phosphat-1 p110alpha phosphorylation of phosphatidylinositol is inhibited by p85ni 655902 N/A 655904 inhibitor inhibitor unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 655905 enzyme target enzyme target substrate substrate unspecified role unspecified role N/A 655906 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false P32871:p.Glu542Lys mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false P32871:p.Glu545Lys mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false P32871:p.Gln546Lys mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction false false false 3 A, D, S3 B These mutations in p110alpha blocked inhibition of kinase activity by p85ni. Binding of IRS-1 phosphotyrosine peptide (from the Tyr608/Tyr628 region) activates wild-type p110alpha/p85ni but not p110-E545K/p85ni. pik3ca-1_phosphat-8 p110alpha phosphorylation of phosphatidylinositol is inhibited by p85ni 655902 N/A 655905 enzyme target enzyme target substrate substrate unspecified role unspecified role N/A 655906 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection N/A 655904 inhibitor inhibitor unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false P27986:p.Arg340Glu mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false P27986:p.Lys379Glu mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction false false false 3 B, C These mutations in p85alpha disrupt its ability to act as an inhibitor of lipid kinase activity of p110alpha. The loss of inhibition for R340E and K379E suggests that these residues are involved in an inhibitory contact with p110alpha. pik3ca-1_phosphat-2 p110alpha phosphorylation of phosphatidylinositol is inhibited by p85ni 655902 N/A 655904 inhibitor inhibitor unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false P27986:p.Lys379Glu mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 655905 enzyme target enzyme target substrate substrate unspecified role unspecified role N/A 655906 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false P32871:p.Glu545Lys mutation mutation mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction false false false 3 C The loss of inhibition for R340E and K379E suggests that these residues are involved in an inhibitory contact with the catalytic subunit. Consistent with this, the p85ni-K379E mutant inhibits the p110a-E545K oncogenic mutant, whereas the wildtype p85ni does not, suggesting that the charge reversal has reestablished the critical inhibitory interaction. pik3ca-1_phosphat-3 p110alpha phosphorylates phosphatidylinositol 655902 N/A 655905 enzyme target enzyme target substrate substrate unspecified role unspecified role N/A 655906 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction false false false 3 C pik3ca-pik3r1-5 Crystal structure of bovine p110alpha ABD and human p85alpha iSH2 655903 N/A 655904 unspecified role unspecified role neutral component neutral component arg534 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false glu496 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false region iSH2 domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 655906 unspecified role unspecified role neutral component neutral component arg79 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false n-terminal ABD sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false glu23 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) 655942 655939 655944 655938 direct interaction direct interaction false false false 1, 2, Table S1 2.4 A working 23.3%, free 29.2%